Biomedical subjects
Publications and source records attributed to Lauren B Krupp.
Fatigue is a common problem in Parkinson's disease (PD), often the most troubling of all symptoms. It is poorly understood, generally under-recognized, and has no known treatment. This article reviews what is known about the symptom, putting it into the context of fatigue in other disorders, and outlines a program for developing better understanding and therapy.
Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer's disease, but their cognitive benefits may extend to additional disorders such as multiple sclerosis (MS). A single-center double-blind placebo-controlled randomized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties. Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in total recall on the Selective Reminding Test, a measure of verbal learning and memory. Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery, patient-reported change in memory, and physician-reported impression of cognitive change. Donepezil improved memory performance on the SRT compared to placebo. This benefit remained significant after controlling for various covariates including Expanded Disability Status Scale (EDSS), MS subtype, interferon beta use, treatment group beliefs, gender, baseline selected reminding test (SRT) score, and reading ability. Subjects on donepezil were more likely to report memory improvement (65.7%) than those on placebo (32.4%). The clinician also reported cognitive improvement in more donepezil (54.3%) than placebo (29.4%) subjects. No serious adverse events related to study medication occurred. However, more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams. Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial. Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention.
An increasing number of children and adolescents with multiple sclerosis (MS) are being identified and treated with disease-modifying therapies. Yet, there currently is little experience to guide clinicians. As more rapid diagnosis is made possible with magnetic resonance imaging, the number of pediatric MS patients requiring treatment will increase with time. This review draws on information from adult and pediatric neurology sources and summarizes current available data. Additional research is clearly needed. Nonetheless, there are several treatment principles: 1) establishing the diagnosis by differentiating MS from acute disseminated encephalomyelitis or recurrent acute disseminated encephalomyelitis; 2) emphasizing that there are parallels between adult and pediatric MS regarding the clinical presentation, disease course, and ability to tolerate therapy (the more extensive experience in adult MS can be applied to most pediatric cases); 3) explaining the importance of starting treatment early in the disease course and that these therapies seem well-tolerated in children; 4) providing reassurance that the family is not alone; as approximately 5% of the MS population has symptom onset before age 18 years (experience with pediatric MS is growing and centers with pediatric MS programs exist in other countries and are developing within the United States); and 5) reviewing symptom management and addressing issues such as academic performance that are unique to the pediatric MS subpopulation.
Fatigue is a significant factor in the lives of many MS patients and the most commonly reported symptom in many studies. Fatigue is an important symptom to consider because it affects patients' social lives, occupations, and activities of daily living. Efforts to predict fatigue have been mixed, but it appears to be related to overall quality of life and mood. From a pathophysiologic perspective, fatigue in MS is multifactorial and complex,involving dysregulation of the immune system, changes in the nervous system related to the disease process, neuroendocrine and neurotransmitter changes, and other factors such as physical deconditioning, sleep disturbance, pain, and medication side effects. Various attempts to assess fatigue have been made, and many measures are now available for use in clinical practice and research. In clinical practice, these measures help guide treatment considerations. Recent research has provided valuable strategies to ameliorate fatigue in MS, and although many patients continue to experience fatigue despite interventions, many receive substantial relief.Nonpharmacologic approaches-considered the first step in treatment-include exercise programs, cooling, dietary considerations, and energy conservation strategies. For patients who continue to experience significant fatigue, several medications (although not specifically approved for use in the reduction of MS-related fatigue) have proved effective in this regard.The first-line agents include amantadine for mild fatigue and modafinil for more severe cases. Second-line agents include pemoline and antidepressant medications. Other pharmacologic agents have also shown some promise.
The relation between self-reported cognitive dysfunction and neuropsychological performance over 24 weeks was assessed in a sample of 53 multiple sclerosis patients. Subjects were assessed at Weeks Zero and 24 as part of a clinical trial to enhance cognition. At baseline, subjects had at least mild cognitive impairment on the Rey Auditory Verbal Learning Test and an absence of depression. Neuropsychological performance was assessed with a modification of the well standardized Brief Repeatable Battery. The 5-item Perceived Deficits Questionnaire and a 2-item memory and attention/concentration questionnaire assessed self-perceived cognitive impairment. Self-assessed cognition did not correlate with neuropsychological performance at either baseline or 24 weeks. However, changes in the self-assessment measures did correlate with changes in neuropsychological performance. Patients accurately perceived some changes in their level of cognitive dysfunction, though they were insensitive to the degree of their current dysfunction. Possible explanations of this pattern of results are discussed.
Healthy control participants (46 women, M age=44.3 yr., SD=7.6; 29 men) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme isease. Participants were selected using Mitofsky-Waksberg random digit dialing. The Buschke 12-word, six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex. Performance on alternate forms of this measure were examined. Mean education, intelligence quotient, and Wide Range Achievement Test-3 Reading scores are reported.
Fatigue is a common disabling symptom of multiple sclerosis (MS). It is often considered a state of exhaustion distinct from depressed mood or physical weakness. Fatigue can be assessed by either self-report scales or performance-based measures; however, neither method captures all features of fatigue. Fatigue in MS frequently leads to unemployment. It is associated with a sense of loss of control over one's environment, low positive affect, psychological distress and neurological impairment. To date there is no reproducible neuroimaging marker or biological correlate that has been identified. Proposed pathological mechanisms of fatigue in MS include neuronal factors such as dysfunction of premotor, limbic, basal ganglia or hypothalamic areas; disruption of the neuroendrocrine axis leading to low arousal; alteration in serotoninergic pathways; changes in neurotransmitter levels; and altered CNS functioning caused by a disruption of the immune response. Treatment of fatigue is best approached in a multidisciplinary fashion that incorporates nonpharmacological interventions as well as medication. Amantadine and modafinil are among the most commonly used medications for fatigue associated with MS. Both medications have been studied with positive results in controlled clinical trials. Additional research towards measurement and pathogenesis of fatigue will hopefully lead to improved therapies.
The symptoms that affect individuals with MS are diverse and change over time. Addressing symptoms in a multidisciplinary fashion and helping patients address problems as they occur are the major elements of symptom management. Successful management involves treating not only the more readily recognized manifestations of MS but also the less apparent MS features, including fatigue, cognitive loss, mood disturbance, and pain. Management of these symptoms is reviewed.